Prognostic value of PEA3 subfamily gene expression in cholangiocarcinoma

BACKGROUND Cholangiocarcinoma(CCA)is a lethal malignancy with limited treatment options and poor prognosis.The PEA3 subfamily of E26 transformation specific genes:ETV1,ETV4,and ETV5 are known to play significant roles in various cancers by influencing cell proliferation,invasion,and metastasis.AIM To analyze PEA3 subfamily gene expression levels in CCA and their correlation with clinical parameters to determine their prognostic value for CCA.METHODS The expression levels of PEA3 subfamily genes in pan-cancer and CCA data in the cancer genome atlas and genotype-tissue expression project databases were analyzed with R language software.Survival curve and receiver operating characteristic analyses were performed using the SurvMiner,Survival,and Procr language packages.The gene expression profiling interactive analysis 2.0 database was used to analyze the expression levels of PEA3 subfamily genes in different subtypes and stages of CCA.Web Gestalt was used to perform the gene ontology/Kyoto encyclopedia of genes and genomes(GO/KEGG)analysis,and STRING database analysis was used to determine the genes and proteins related to PEA3 subfamily genes.RESULTS ETV1,ETV4,and ETV5 expression levels were significantly increased in CCA.There were significant differences in ETV1,ETV4,and ETV5 expression levels among the different subtypes of CCA,and predictive analysis revealed that only high ETV1 and ETV4 expression levels were significantly associated with shorter overall survival in patients with CCA.GO/KEGG analysis revealed that PEA3 subfamily genes were closely related to transcriptional misregulation in cancer.In vitro and in vivo experiments revealed that PEA3 silencing inhibited the invasion and metastasis of CCA cells.CONCLUSION The expression level of ETV4 may be a predictive biomarker of survival in patients with CCA.

Genome-Wide Identification of ABCC Gene Subfamily Members and Functional Analysis of CsABCC11 in Camellia sinensis

The ATP-binding cassette(ABC)transporter is a gene superfamily in plants.ATP-binding cassette subfamily C(ABCC)protein is a multidrug resistance-associated(MRP)transporter.They play various roles in plant growth,development,and secondary metabolite transport.However,there are few studies on ABCC transporters in tea plants.In this study,genome-wide association study(GWAS)analysis of epigallocatechin gallate(EGCG)content in 108 strains of Kingbird revealed that CsABCCs may be involved in EGCG transport.We identified 25 CsABCC genes at the genomic level of the tea plant,their phylogenetic tree,gene structure,targeted miRNA and other bioinformatics were analyzed.The expression patterns of CsABCCs in eight different tissues and abiotic stress indicate that they have potential roles in regulating the growth,development,and defense of tea plants.The correlation analysis revealed that the expression of the CsABCC11 gene was closely related to the EGCG content in tea buds of 108 strains of the Kingbird,and the subcellular localization experiments in tobacco showed that CsABCC11 protein was localized on the plasma membrane.The virus-induced gene silencing(VIGS)strategy in tea plants further verified that CsABCC11 was involved in EGCG accumulation.Our study laid a foundation for studying the biological function of CsABCC and provided a new candidate molecular marker gene for further EGCG-related variety breeding,which will be of great interest to breeders.

Genome-wide analysis of the B3 transcription factors reveals that RcABI3/VP1 subfamily plays important roles in seed development and oil storage in castor bean(Ricinus communis)

The B3 transcription factors(TFs)in plants play vital roles in numerous biological processes.Although B3 genes have been broadly identified in many plants,little is known about their potential functions in mediating seed development and material accumulation.Castor bean(Ricinus communis)is a non-edible oilseed crop considered an ideal model system for seed biology research.Here,we identified a total of 61 B3 genes in the castor bean genome,which can be classified into five subfamilies,including ABI3/VP1,HSI,ARF,RAV and REM.The expression profiles revealed that RcABI3/VP1 subfamily genes are significantly up-regulated in the middle and later stages of seed development,indicating that these genes may be associated with the accumulation of storage oils.Furthermore,through yeast one-hybrid and tobacco transient expression assays,we detected that ABI3/VP1 subfamily member RcLEC2 directly regulates the transcription of RcOleosin2,which encodes an oil-body structural protein.This finding suggests that RcLEC2,as a seed-specific TF,may be involved in the regulation of storage materials accumulation.This study provides novel insights into the potential roles and molecular basis of B3 family proteins in seed development and material accumulation.

A New Subfamily of Aphids (Hemiptera,Aphidomorpha) from the Early Cretaceous Lebanese Amber with a Description of the Oldest Apterous Morphs

Aphids are marked by their high polymorphism, but species reported from the Early Cretaceous are known only from alate morphs. The discovery of an apterous adult morph in Lebanese amber and a larva of the same species are very important for the understanding of both the morphological and biological evolution of this insect group at the very early stage of development. Gondvanoaphis estephani new subfamily, new genus and species of the recent aphids family Thelaxidae is described. The characters of the new genus in respect to other genera placed in Thelaxidae are reviewed. The palaeoeeological and palaeogeographical data concerning Gondvanoaphis new genus are also discussed.

Cathepsin L, transmembrane peptidase/serine subfamily member 2/4, and other host proteases in COVID-19 pathogenesis – with impact on gastrointestinal tract

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)seems to employ two routes of entrance to the host cell;via membrane fusion(with the cells expressing both angiotensin converting enzyme 2(ACE2)and transmembrane peptidase/serine subfamily member 2/4(TMPRSS2/4))or via receptor-mediated endocytosis(to the target cells expressing only ACE2).The second mode is associated with cysteine cathepsins(probably cathepsin L)involvement in the virus spike protein(S protein)proteolytic activation.Also furin might activate the virus S protein enabling it to enter cells.Gastrointestinal tract(GIT)involvement in SARS-CoV-2 infection is evident in a subset of coronavirus disease 2019(COVID-19)patients exhibiting GIT symptoms,such as diarrhea,and presenting viral-shedding in feces.Considering the abundance and co-localization of ACE2 and TMPRSS2 in the lower GIT(especially brush-border enterocytes),these two receptors seem to be mainly involved in SARS-CoV-2 invasion of the digestive tract.Additionally,in vitro studies have demonstrated the virions capability of infection and replication in the human epithelial cells lining GIT.However,also furin and cysteine cathepsins(cathepsin L)might participate in the activation of SARS-CoV-2 spike protein contributing to the virus invasiveness within GIT.Moreover,cathepsin L(due to its involvement in extracellular matrix components degradation and remodeling,the processes enhanced during SARS-CoV-2-induced inflammation)might be responsible for the dysregulation of absorption/digestion functions of GIT,thus adding to the observed in some COVID-19 patients symptoms such as diarrhea.

Cytochrome P450 family 17 subfamily A member 1 mutation causes severe pseudohermaphroditism: A case report

BACKGROUND 17α-Hydroxylase deficiency(17-OHD)is a rare form of congenital adrenal hyperplasia,characterized by hypertension,hypokalemia,and gonadal dysplasia.However,due to the lack of a comprehensive understanding of this disease,it is prone to misdiagnosis and missed diagnosis,and there is no complete cure.CASE SUMMARY We report a female patient with 17-OHD.The patient was admitted to the Department of Neurology of our hospital due to limb weakness.During treatment,it was found that the patient’s condition was difficult to correct except for hypokalemia,and her blood pressure was difficult to control with various antihypertensive drugs.She was then transferred to our department for further treatment.On physical examination,the patient's gonadal development was found to be abnormal,and chromosome analysis demonstrated karyotype 46,XY.Considering the possibility of 17-OHD,the cytochrome P450 family 17 subfamily A member 1(CYP17A1)test was performed to confirm the diagnosis.CONCLUSION The clinical manifestations of 17-OHD are complex.Hormone determination,imaging examination,chromosome determination and CYP17A1 gene test are helpful for early diagnosis.

A Note on Determine the Greatest Common Subfamily of Two NFSRs by Grbner Basis

For nonlinear feedback shift registers （NFSRs）, their greatest common subfamily may be not unique. Given two NFSRs, the authors only consider the case that their greatest common subfamily exists and is unique. If the greatest common subfamily is exactly the set of all sequences which can be generated by both of them, the authors can determine it by Grobner basis theory. Otherwise, the authors can determine it under some conditions and partly solve the problem.

Blockade of transient receptor potential cation channel subfamily V member 1 promotes regeneration after sciatic nerve injury

The transient receptor potential cation channel subfamily V member 1（TRPV1） provides the sensation of pain（nociception）. However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517（300 mg/kg）, a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immunofluorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clusters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.

NR4A1 silencing alleviates high-glucose-stimulated HK-2 cells pyroptosis and fibrosis via hindering NLRP3 activation and PI3K/AKT pathway

BACKGROUND The pathophysiology of diabetic kidney disease(DKD)is complex.Interfering with the processes of pyroptosis and fibrosis is an effective strategy for slowing DKD progression.Previous studies have revealed that nuclear receptor subfamily 4 group A member 1(NR4A1)may serve as a novel pathogenic element in DKD;however,the specific mechanism by which it contributes to pyroptosis and fibrosis in DKD is unknown.AIM To investigate the role of NR4A1 in renal pyroptosis and fibrosis in DKD and possible molecular mechanisms.METHODS Streptozotocin 60 mg/kg was injected intraperitoneally to establish a rat model of DKD.Typically,45 mmol/L glucose[high glucose(HG)]was used to activate HK-2 cells to mimic the DKD model in vitro.HK-2 cells were transfected with NR4A1 siRNA to silence NR4A1.RESULTS NR4A1 was elevated in renal tissues of DKD rats and HG-stimulated HK-2 cells.Concurrently,NOD-like receptor protein 3(NLRP3)and phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)pathways were triggered,and pyroptosis and expression of fibrosis-linked elements was increased in vivo and in vitro.These alterations were significantly reversed via NR4A1 silencing.CONCLUSION Inhibition of NR4A1 mitigated pyroptosis and fibrosis via suppressing NLRP3 activation and the PI3K/AKT pathway in HG-activated HK-2 cells.

Distinct structural characteristics define a new subfamily of Mycoplasma ferritin

Ferritins can generally be divided into four subfamilies based on their structural characteristics,namely,the classic ferritins(Ftns),bacterioferritins(Bfrs),DNA-binding proteins from starved cells(Dps’),and encapsulated ferritins(Enc Ftns).However,the ferritin from Mycoplasma penetrans(Mpef)possesses a particular ferroxidase center with an extreme low activity and exhibits unusual characteristics,indicating that it could be a member of a quite different subfamily of ferritins.Hereby,the crystal structure of the ferritin from Ureaplasma urealyticum(Uurf)is presented,Mpef and Uurf have very similar properties,though they display very low sequence similarity.Thus,ferritins from Mycoplasma with these unique properties do not belong to any known subfamily,but they should rather be placed in a novel ferritin subfamily,which we term Mycoplasma Ferritin(Mfr).

The classification of ATP-binding cassette subfamily A member 3 mutations using the cystic fibrosis transmembrane conductance regulator classification system

Importance: The ATP-binding cassette subfamily A member 3 (ABCA3) protein plays a vital role in surfactant homeostasis. Mutations in the ABCA3 gene lead to the development of interstitial lung disease. In the most severe manifestation, mutations can lead to a fatal respiratory distress syndrome in neonates. ABCA3 belongs to the same ATP-binding cassette transporter superfamily as the cystic fibrosis transmembrane conductance regulator (CFTR), the gene that causes cystic fibrosis. Objective: To classify ABCA3 mutations in a manner similar to CFTR mutations in order to take advantage of recent advances in therapeutics. Methods: Sequence homology between the CFTR protein and the ABCA3 protein was established. The region of CFTR that is a target for the new potentiator class of drugs was of particular interest. We performed a literature search to obtain all published mutations that were thought to be disease causing. We classified these mutations using the established CFTR classification system. When possible, we drew on previous experimental classification of ABCA3 mutations. Results: Although the proteins share the same overall structure, only a 19％identity was established between CFTR and ABCA3. The CFTR therapeutic target region has a 22％ homology with the corresponding ABCA3 region. Totally 233 unique protein mutations were identified. All protein mutations were classified and mapped to a schematic diagram of the ABCA3 protein. Interpretation: This new classification system for ABCA3, based on CFTR classification, will likely aid further research of clinical outcomes and identification of mutation-tailored therapeutics, with the aim for improving clinical care for patients with ABCA3 mutations.

A new subfamily of the grasshopper （Orthoptera： Acridoidea： Gomphoceridae） from the Tibetan Plateau of China

This paper reports a new subfamily, a new genus and a new species, that is, Pacrinae subfam, nov., Pacris gen. nov and Pacris xizangensis sp. nov in Gomphoceridae. The new subfamily is allied to Orinhippinae of Gomphoeeridae and it differs from the latter by wings and tympanum absent. The new genus is similar to Orinhippus Uvarov, 1921 but differs from the latter in： （i） foveolae absent; （ii） tegmina absent; （iii） tympanum absent; （iv） hind margin of pronotum with incised in the middle. Type specimens are deposited in the Museum of Hebei University, Baoding, China.

Computational identification and evolutional analysis of Piwi subfamily in 11 Drosophila species

The complete genome sequences of 11 Drosophila species provide an opportunity to investigate the gene family evolution in closely related species. Drosophila Piwi subfamily, including three members, piwi, Aub and Ago3, has attracted increasing attention as it participates in the biogenesis of piRNA. Here, we identified 33 Piwi homologs from the genome of 11 Drosophila species. The full-length cDNA sequences ofpiwi and Aub genes were obtained by using New GENSCAN Web Server. The Ago3 homologs were difficult regarding full-length information because they had long introns. The genomic structure of Piwi subfamily genes are highly conserved among diverse Drosophila species. Insect piwi and Aub genes have long first introns. The average length of the first intron is 1 284 bp for piwi and 840 bp for Aub, which is much larger than those of other introns （93 bp for Piwi and 54 bp for Aub）. However, this phenomenon is not observed in mammalian piwi genes. We also found that there were abundant repeat sequences in both exons and introns of insect Ago3 genes. Due to recent insertions of long terminal repeat elements in four Drosophila species, part of the third introns exhibit higher conservation than adjacent exons and other introns. An evolutional tree created by Minimum Evolution method indicates that mammalian piwi genes are more closely related to the insect Ago3 Piwi subfamily.

The expression of T-cell receptor Vβ subfamily in hepatitis B virus-related acute-on-chronic liver failure patients and its clinical significance

Objective To investigate the expression and clinical significance of T-cell receptor(TCR)Vβsubfamily in hepatitis B virus(HBV)-related acute-on-chronic liverfailure(HBV-ACLF)patients.Methods Twenty-eight patients with HBV-ACLF(HBV-ACLF group)and 32patients with chronic hepatitis B flare(CHB-F group),who were treated in The Second People’s Hospital

Association of polymorphisms of potassium voltage-gated channel,KQT-like subfamily,member 1 and type 2 diabetes in Jiangsu province,China

Objective To study the association of polymorphisms in the potassium voltage-gated channel,KQT-like subfamily,member 1 (KCNQ1) gene with type 2 diabetes in Chinese population from Jiangsu province.Methods Subjects consisting of 2925 cases and 3281 controls

Elevated ETV4 expression in cholangiocarcinoma is linked to poor prognosis and may guide targeted therapies

Cholangiocarcinoma(CCA),a highly aggressive bile duct cancer,is associated with late-stage diagnosis and limited treatment options,leading to poor patient outcomes.Early detection and personalized treatment strategies are crucial.The study by Wang et al highlights the prognostic potential of the PEA3 subfamily genes(ETV1,ETV4,and ETV5)in CCA,identifying ETV4 as a particularly promising biomarker.Their bioinformatic analysis revealed that elevated ETV4 expression correlates with poorer survival,positioning it as a strong indicator of disease progression.These findings suggest that ETV4 could enhance prognostic precision and guide personalized therapies,although further validation through large-scale clinical trials is essential.Challenges in clinical application include the need for comprehensive experimental validation and addressing the tumor heterogeneity in CCA.Future research should focus on validating these biomarkers in diverse cohorts and developing targeted therapies,especially in regions where CCA is endemic.

Targeting NR1D1 in organ injury:challenges and prospects

Nuclear receptor subfamily 1,group D,member 1(NR1D1,also known as REV-ERBα)belongs to the nuclear receptor(NR)family,and is a heme-binding component of the circadian clock that consolidates circadian oscillators.In addition to repressing the transcription of multiple clock genes associated with circadian rhythms,NR1D1 has a wide range of downstream target genes that are intimately involved in many physiopathological processes,including autophagy,immunity,inflammation,metabolism,and aging in multiple organs.This review focuses on the pivotal role of NR1D1 as a key transcription factor in the gene regulatory network,with particular emphasis on the milestones of the latest discoveries of NR1D1 ligands.NR1D1 is considered as a promising drug target for treating diverse diseases and may contribute to research on innovative biomarkers and therapeutic targets for organ injury-related diseases.Further research on NR1D1 ligands in prospective human trials may pave the way for their clinical application in many organ injury-related disorders.

Cloning of a MADS Box Gene(GhMADS3)from Cotton and Analysis of Its Homeotic Role in Transgenic Tobacco

A MADS box gene （GhMADS3） was cloned from cotton （Gossypium hirsutum L.） based on EST sequences. The predicted protein sequence of GhMADS3 showed 85%, 73%, and 62% identity with Theobroma cacao TcAG, Antirrhinum majus FAR, and Arabidopsis thaliana AG, respectively, and was grouped with AG homologues when the full length sequences excluding N-extensions were compared. GhMADS3 expressed in the wild type cotton flower primarily in stamens and carpels, which was comparable to AG in Arabidopsis. However, it was not expressed in floral buds of a homeotic cotton variant chvl. Ectopic expression of GhMADS3 in tobacco （Nicotiana tabacum L.） resulted in flowers with sepal-to-carpel and petal-to-stamen transformation. The carpelloid first whorl organs, with stigmatic tissue on their upper edges, had a white appearance when compared with the dark green color of the wild type sepals. At times, long filaments were observed at the fusion site of the first carpelloid oranges. The second whorl organs in staminoid were usually smaller than the wild type and the color was changed from pink to white. These results suggest that GhMADS3 has a homeotic role in flower development.

Phylogenetic Reconstruction of the Family Acrypteridae (Orthoptera: Acridoidea) Based on Mitochondrial Cytochrome b Gene

Sequences from the mitochondrial cytochrome b gene （Cyt b） were determined for 25 species from the superfamily Acridoidae and the homologous sequences of 19 species of grasshoppers were downloaded from the GenBank data library. The purpose was to develop a molecular phylogeny of the Acrypteridae, and to interpret the phylogenetic position of the family within the superfamily Acridoidea. Phylogeny was reconstructed by Maximum-parsimony （MP） and Bayesian criteria using Yunnanites coriacea and Tagasta marginella as outgroups. The alignment length of the fragments was 384 bp after excluding ambiguous sites, including 167 parsimony informative sites. In the fragments, the percentages of A ＋ T and G ＋ C were 70.7% and 29.3%, respectively. The monophyly of Arcypteridae is not supported by phylogenetic trees. Within the Arcypteridae, neither Arcypterinae nor Ceracrinae is supported as a monophyletic group. The current genus Chorthippus is not a monophyletic group, and should be a polyphyletic group. The present results are significantly different from the classification scheme of Arcypteridae, which is based on morphology.

Mitofusin2 Decreases Intracellular Cholesterol of Oxidized LDL-Induced Foam Cells from Rat Vascular Smooth Muscle Cells

Mitofusin2 （Mfn2） plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells （VSMCs）. The purpose of this study was to investigate the effects of Mfn2 on the traffick- ing of intracellular cholesterol in the foam ceils derived from rat VSMCs （rVSMCs） and also to investigate the effects of Mfn2 on the expression of adenosine triphosphate-binding cassette subfamily A member 1 （ABCA1）, adenosine triphosphate-binding cassette subfamily G member 1 （ABCG1） and peroxisome proliferator-activated receptor gamma （PPARy）. The rVSMCs were co-cultured with oxi- dized low density lipoprotein （LDL, 80 ~tg/mL） to produce foam cells and cholesterol accumulation in cells. Before oxidized LDL treatment, different titers （20, 40 and 60 pfu/cell） of recombinant adenovirus containing Mfn2 gene （Adv-Mfn2） were added into the culture medium for 24 h to transfect the Mfn2 gene into the rVSMCs. Then the cells were harvested for analyses. The protein expression of Mfn2 was significantly higher in Adv-Mfn2-transfected group than in untransfected group （P〈0.05）, and the ex- pression levels significantly increased when the titer of Adv-Mfn2 increased （P〈0.05）. At 24 or 48 h af- ter oxidized LDL treatment, rVSMCs became irregular and their nuclei became larger, and their plasma abounded with red lipid droplets. However, the number of red lipid droplets was significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group. At 48 h after oxidized LDL treatment, the intracellular cholesterol in rVSMCs was significantly increased （P〈0.05）, but it was sig- nificantly decreased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）, and it also significantly decreased when the titer of Adv-Mfn2 increased （P〈0.05）. The mRNA and pro- tein expression levels of ABCA1 and ABCG1 were significantly increased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）. Though the mRNA and protein expression levels of PPARy was not significantly increased （P〉0.05）, the phosporylation levels of PPARy were signifi- cantly decreased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）. These results suggest that the transfection of Adv-Mfn2 can significantly reduce intracellular cholesterol in oxidized LDL-induced rVSMCs possibly by decreasing PPAR＇/phosporylation and then increasing pro- tein expression levels of ABCAI and ABCG1, which may be helpful to suppress the formation of foam cells.